14 Sept 2020

Schizophrenia outcomes may be improved by repurposed drug

A clinical trial is recruiting women with schizophrenia
A study by Monash University researchers has found that a drug used in the treatment of osteoporosis may help improve symptoms of schizophrenia. 
Professor Jayashri Kulkarni, Monash University, Central Clinical School, pioneered the use of estrogens in the treatment of schizophrenia and has conducted ground-breaking research in this area for the past 25 years. She and colleague Professor Suresh Sundram at the School of Clinical Sciences at Monash Health, are leading an ongoing clinical trial of a new type of ‘brain estrogen’ called a Selective Estrogen Receptor Modulator (SERM). 
Bazedoxifene is the new SERM being trialled and early results show improvement in schizophrenia symptoms. 
Adding to the clinical work, world-first preclinical studies conducted by a team from Monash University, School for Clinical Sciences, showed the drug bazedoxifene can improve spatial memory in a mouse model. 
The research, led by Dr Rachel Hill and recently published in the journal Psychoneuroendocrinology, also won the Curt Richter Award from the International Society of Psychoneuroendocrinology in August. 
Dr Hill, whose research focuses on schizophrenia, said up to 40 per cent of people with the illness do not respond completely to available treatments. “No treatment currently tackles the biology of schizophrenia to comprehensively treat the key symptoms of delusions, hallucinations and memory impairments,” Dr Hill said. 
Because women have an onset of schizophrenia later than men, and relapse at menopause, Professor Kulkarni was prompted to study the role of oestrogen in the disorder. Building on her initial studies of estradiol treatment in women, Professor Kulkarni and colleagues conducted clinical trials of an early SERM, raloxifene and found improvement in psychosis symptoms. 
They are following up this lead with the latest SERM – bazedoxifene. Bazedoxifene selectively triggers oestrogen receptors without unwanted side effects, on breast, uterus and ovarian tissue. It is used in the treatment of osteoporosis in menopausal women. 
Dr Hill and her team are the first to show that the drug crosses the blood-brain barrier and activates the main oestrogen receptors in the brain and improves spatial memory. 
“In people with schizophrenia, the area in the brain associated with spatial memory has dysfunctional wiring,” she said. “We believe this drug may act like a metronome, bringing all the brain’s firing into sync.” 
 The preclinical study showed the drug improved spatial memory in mice with cognitive impairment similar to that seen regarding spatial memory in schizophrenia .  
Clinical trials have started at Monash Alfred Psychiatry Research Centre and Monash Medical Centre testing the drug in women with schizophrenia. To find out more about the trial: Reference
Hill RA, Kouremenos K, Tull D, et al. Bazedoxifene - a promising brain active SERM that crosses the blood brain barrier and enhances spatial memory. Psychoneuroendocrinology. 2020;121:104830. doi:10.1016/j.psyneuen.2020.104830 
This research was featured in The Australian 14 Sept 2020
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